Is DBT p.Lys313Asn (c.939G>C) pathogenic?

DBT p.Lys313Asn (c.939G>C) is classified Pathogenic in DBT (ClinVar, Multiple submitters, 8 submitters; last evaluated 2024-12-19). AlphaMissense: likely pathogenic (0.9965); Very rare (popmax 0.00549%, sas); Associated with maple syrup urine disease type 2.

What condition is associated with DBT p.Lys313Asn (c.939G>C)?

DBT p.Lys313Asn (c.939G>C) is associated with maple syrup urine disease type 2, maple syrup urine disease, maple syrup urine disease type 1A (ClinVar).

How common is DBT p.Lys313Asn (c.939G>C) in the general population?

DBT p.Lys313Asn (c.939G>C) is very rare (popmax 0.00549%, sas) (gnomAD).

How is Maple syrup urine disease inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about DBT p.Lys313Asn (c.939G>C)?

AlphaMissense predicts likely pathogenic (score 0.9965) — an in-silico prediction, not a clinical call.

DBT p.Lys313Asn

c.939G>C · rs398123676 · VCV94017

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.9965 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

maple syrup urine disease type 2

Computational evidence

Protein change
AlphaMissense	0.9965	likely pathogenic ✓ concordant with ClinVar · top 2% in DBT
REVEL	0.586	indeterminate
SaProt	LLR -14.76	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	Δ0.28	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.49	loss · gain 0.03 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 2.2	GERP 0.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 54 kb · p 0.0036 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,076 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000411% 6/1,461,604 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,215
Remaining individualsnot grpmax-eligible	0.0016%	62,498

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DBT
Protein: p.Lys313Asn
Coding: c.939G>C
MANE Select: NM_001918
dbSNP: rs398123676
Type: single nucleotide variant
Location: chr1:100214817 (GRCh38)
Gene constraint: LOEUF 1.255 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.71 · 5 PDB

Full DBT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

maple syrup urine disease type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: maple syrup urine disease maple syrup urine disease type 1A

For Maple syrup urine disease (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

DBT p.Lys313= Uncertain significance ★ same residue
DBT c.1018-550A>G Pathogenic/Likely pathogenic ★★ same condition
DBT c.1281+1G>A Pathogenic/Likely pathogenic ★★ same condition
DBT c.1281+1G>T Pathogenic/Likely pathogenic ★★ same condition
DBT c.51+1G>T Pathogenic/Likely pathogenic ★★ same condition
DBT c.52-1G>A Pathogenic/Likely pathogenic ★★ same condition
DBT c.773-2A>G Pathogenic ★★ same condition
DBT p.Arg169Ter Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dbt-p-lys313asn (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown